(Baldwin et al., 1991; Rassnick et al., 1993; Valdez et al., 2003) administration of CRF receptor antagonists. This effect appears to be mediated by CRF1 receptors (Overstreet et al., 2004), although a role for CRF2 receptors cannot be ruled out (Valdez et al., 2004). Together, these findings indicate that chronic alcohol exposure and withdrawal experience can be viewed as a potent stressor that disrupts the functional integrity of the HPA axis while at the same time recruiting and sensitizing extra-hypothalamic CRF systems. The resultant allostatic state is characterized by progressive dysregulation of neuroendocrine and brain stress systems along with perturbations in brain reward pathways that contribute to dysphoric and negative affect associated with alcohol dependence. Implications of these changes regarding motivation for alcohol self-administration as well as relapse vulnerability are discussed below.
